The Purkinje wayer of de cerebewwum, which contains de ceww bodies of de Purkinje cewws and Bergmann gwia, express a warge number of uniqwe genes.[4] Purkinje-specific gene markers were awso proposed by comparing de transcriptome of Purkinje-deficient mice wif dat of wiwd-type mice.[5] One iwwustrative exampwe is de Purkinje ceww protein 4 (PCP4) in knockout mice, which exhibit impaired wocomotor wearning and markedwy awtered synaptic pwasticity in Purkinje neurons.[6][7] PCP4 accewerates bof de association and dissociation of cawcium (Ca2+) wif cawmoduwin (CaM) in de cytopwasm of Purkinje cewws, and its absence impairs de physiowogy of dese neurons.[6][7][8][9]

There is evidence in mice and humans dat bone marrow cewws eider fuse wif or generate cerebewwar Purkinje cewws, and it is possibwe dat bone marrow cewws, eider by direct generation or by ceww fusion, couwd pway a rowe in repair of centraw nervous system damage.[10][11][12][13][14] Furder evidence points yet towards de possibiwity of a common stem ceww ancestor among Purkinje neurons, B-wymphocytes and awdosterone-producing cewws of de human adrenaw cortex.[13]

The Purkinje ceww protein 4 (PCP4) is markedwy immunoreactive in de Purkinje cewws of de human cerebewwum. From top to bottom 40X, 100X and 200X microscopic magnifications. The immunohistochemistry was performed based on pubwished medods.[6]

Purkinje cewws show two distinct forms of ewectrophysiowogicaw activity:

Simpwe spikes occur at rates of 17 – 150 Hz (Raman and Bean, 1999), eider spontaneouswy or when Purkinje cewws are activated synapticawwy by de parawwew fibers, de axons of de granuwe cewws.

Compwex spikes are swow, 1–3 Hz spikes, characterized by an initiaw prowonged warge-ampwitude spike, fowwowed by a high-freqwency burst of smawwer-ampwitude action potentiaws. They are caused by cwimbing fiber activation and can invowve de generation of cawcium-mediated action potentiaws in de dendrites. Fowwowing compwex spike activity, simpwe spikes can be suppressed by de powerfuw compwex spike input.[15]

Purkinje cewws show spontaneous ewectrophysiowogicaw activity in de form of trains of spikes bof sodium-dependent and cawcium-dependent. This was initiawwy shown by Rodowfo Lwinas (Lwinas and Hess (1977) and Lwinas and Sugimori (1980)). P-type cawcium channews were named after Purkinje cewws, where dey were initiawwy encountered (Lwinas et aw. 1989), which are cruciaw in cerebewwar function, uh-hah-hah-hah. We now know dat activation of de Purkinje ceww by cwimbing fibers can shift its activity from a qwiet state to a spontaneouswy active state and vice versa, serving as a kind of toggwe switch.[16] These findings have been chawwenged by a study suggesting dat such toggwing by cwimbing-fiber inputs occurs predominantwy in anaesdetized animaws and dat Purkinje cewws in awake behaving animaws, in generaw, operate awmost continuouswy in de upstate.[17] But dis watter study has itsewf been chawwenged[18] and Purkinje ceww toggwing has since been observed in awake cats.[19] A computationaw modew of de Purkinje ceww has shown intracewwuwar cawcium computations to be responsibwe for toggwing.[20]

Findings have suggested dat Purkinje ceww dendrites rewease endocannabinoids dat can transientwy downreguwate bof excitatory and inhibitory synapses.[21] The intrinsic activity mode of Purkinje cewws is set and controwwed by de sodium-potassium pump.[22] This suggests dat de pump might not be simpwy a homeostatic, "housekeeping" mowecuwe for ionic gradients. Instead, it couwd be a computation ewement in de cerebewwum and de brain, uh-hah-hah-hah.[23] Indeed, a mutation in de Na+-K+ pump causes rapid onset dystonia parkinsonism; its symptoms indicate dat it is a padowogy of cerebewwar computation, uh-hah-hah-hah.[24]
Furdermore, using de poison ouabain to bwock Na+-K+ pumps in de cerebewwum of a wive mouse induces ataxia and dystonia.[25] Numericaw modewing of experimentaw data suggests dat, in vivo, de Na+-K+ pump produces wong qwiescent punctuations (>> 1 s) to Purkinje neuron firing; dese may have a computationaw rowe.[26]Awcohow inhibits Na+-K+ pumps in de cerebewwum and dis is wikewy how it corrupts cerebewwar computation and body co-ordination, uh-hah-hah-hah.[27][28]

In humans, Purkinje cewws can be harmed by a variety causes: toxic exposure, e.g. to awcohow or widium; autoimmune diseases; genetic mutations causing spinocerebewwar ataxias, gwuten ataxia, Unverricht-Lundborg disease, or autism; and neurodegenerative diseases dat are not known to have a genetic basis, such as de cerebewwar type of muwtipwe system atrophy or sporadic ataxias.[29][30]

Gwuten ataxia is an autoimmune disease triggered by de ingestion of gwuten.[31] The deaf of Purkinje cewws as a resuwt of gwuten exposure is irreversibwe. Earwy diagnosis and treatment wif a gwuten-free diet can improve ataxia and prevent its progression, uh-hah-hah-hah.[29][32] Less dan 10% of peopwe wif gwuten ataxia present any gastrointestinaw symptom, yet about 40% have intestinaw damage.[32] It accounts for 40% of ataxias of unknown origin and 15% of aww ataxias.[32]

Some domestic animaws can devewop a condition where de Purkinje cewws begin to atrophy shortwy after birf, cawwed cerebewwar abiotrophy. It can wead to symptoms such as ataxia, intention tremors, hyperreactivity, wack of menace refwex, stiff or high-stepping gait, apparent wack of awareness of foot position (sometimes standing or wawking wif a foot knuckwed over), and a generaw inabiwity to determine space and distance.[34] A simiwar condition known as cerebewwar hypopwasia occurs when Purkinje cewws faiw to devewop in utero or die off before birf.

The genetic conditions ataxia tewangiectasia and Niemann Pick disease type C, as weww as cerebewwar essentiaw tremor, invowve de progressive woss of Purkinje cewws.
In Awzheimer's disease, spinaw padowogy is sometimes seen, as weww as woss of dendritic branches of de Purkinje cewws.[35] Purkinje cewws can awso be damaged by de rabies virus as it migrates from de site of infection in de periphery to de centraw nervous system.[36]